权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Biological function and transcriptional regulation of mouse peptidylarginine deiminase type IV gene, Padi4

小鼠IV型肽基精氨酸脱亚氨酶基因Padi4的生物学功能和转录调控

基本信息

批准号：
16580071
负责人：
TAKAHARA Hidenari
金额：
$ 2.05万
依托单位：
Ibaraki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Peptidylarginine deiminase is a enzyme which convert arginine residues to citrulline residues. We reported that genomics of murine PAD are involved into five gene cluster located in 4E1 region, resembling those of human PAD gene cluster. Recent study disclosed the association of functional haplotypes of the gene PADI4 (orthologue to Padi4) with rheumatoid arthritis. Therefore, function of PAD4 and characterization of the elements regulating PADI4 gene expression using experimental animals is crucial to understanding their involvement in tissue physiology and pathological conditions. We made monoclonal antibodies against murine PAD4 and found the nuclear localization of this enzyme in the peritoneal macrophage by immunohistochemisty of the antibody. Furthermore, pristine introduced into peritoneal cavity of mouse induced the expression of PAD4 gene and deiminated U1-70K peptide of snRNP. These data suggested that the conversion of arginine residues of U1-70K into citrulline residues evokes systemic lupus erythematosus. In fact, the PAD4 could deiminate the peptide of U1-70K, whereas the deimination of p30gag from MLV was not observed. These findings indicated that U1-70K is a specific substrate for PAD4 in the nucleus. Taken together, our research supported by this grant revealed the possible mechanism of autoantibody disease via the deimination of nuclear protein.

肽基精氨酸脱亚胺酶是一种将精氨酸残基转化为瓜氨酸残基的酶。我们报道了小鼠PAD基因组在4 E1区有5个基因簇，与人PAD基因簇相似。最近的研究揭示了Padi 4基因（Padi 4的直向同源物）的功能单倍型与类风湿关节炎的关联。因此，PAD 4的功能和使用实验动物调节PADI 4基因表达的元件的表征对于理解它们参与组织生理学和病理学条件是至关重要的。我们制备了抗小鼠PAD 4的单克隆抗体，并通过抗体的免疫化学方法发现该酶在腹腔巨噬细胞的核内定位。此外，将pristine导入小鼠腹腔可诱导snRNP的PAD 4基因和脱亚氨基U1- 70 K肽的表达。这些数据表明U1- 70 K的精氨酸残基转化为瓜氨酸残基引起系统性红斑狼疮。事实上，PAD 4可以将U1- 70 K的肽段脱亚胺化，而没有观察到来自MLV的p30 gag的脱亚胺化。这些结果表明，U1- 70 K是细胞核中PAD 4的特异性底物。综上所述，我们的研究揭示了自身抗体疾病通过核蛋白脱亚胺化的可能机制。

项目成果

期刊论文数量（29）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Inhibitory effect of mizorubine on matrix metalloproteinase-1 production in synovial fibroblasts and THP-1 macropages

Mizorubine 对滑膜成纤维细胞和 THP-1 巨页中基质金属蛋白酶-1 产生的抑制作用

DOI：
发表时间：
2005
期刊：
Mod Rheumatol 15
影响因子：
0
作者：
Zhong B;Tajima M;Takahara H;Nochi H;Tamoto K;Tamura N;Kobayashi S;Tamura Y;Ikdeda M;Akimoto T;Yoshino S;Hashimoto H
通讯作者：
Hashimoto H

Regulation of the expression of peptidylarginine deiminase type II gene (PADI2) in human keratinocytes involves Sp1 and Sp3 transcription factors